Bacterial superantigens have profound in vivo effects and have been implicated in human diseases such as toxic shock syndrome, adult respiratory distress syndrome (ARDS), and autoimmune disease. In addition, superantigen-secreting strains of Staphylococcus aureus have been associated with unexpected death resulting from influenza virus. A murine model has been developed to study the interplay between the bacterial superantigen, Staphylococcus enterotoxin B (SEB) and influenza infection. Injection of SEB into normal mice has numerous effects, including activation of T cells bearing the relevant T cell receptor (TCR) Vbeta elements, non-specific immune suppression, anergy, apoptosis, and massive cytokine secretion, both by T cells and MHC class II+ presenting cells. Despite these dramatic in vivo effects, bacterial superantigens are not lethal in mice. However, injection of SEB into mice 7 days after non- lethal infection with influenza virus results in the rapid onset of death. The experiments proposed here are designed to understand the role of viral infection in sensitizing mice to the lethal effects of SEB, and, in a broader sense, to determine the effects of superantigen on a concurrent immune response to infectious virus. This is of clinical relevance, because secondary bacterial infections are commonly associated with viruses that cause pathology in the respiratory tract.